Excitotoxicity may contribute to neuronal and synaptic loss in Alzheimer's disease (AD). Aberrant levels of gephyrin, a post-synaptic receptor-stabilizing protein, could affect the inhibitory modulation of excitatory impulses. We assayed gephyrin protein in two brain areas susceptible to neuronal loss in AD, and in a spared area, in autopsy tissue from normal subjects (n = 15) and AD patients (n = 15). Quantification was by in-gel immunodetection against known concentrations of a recombinant truncated gephyrin standard. Gephyrin abundance was significantly reduced (P < 0.01) in AD. Area-wise analysis showed that gephyrin levels were reduced in both spared and susceptible regions, indicating a global phenomenon. When samples were categorized on an index of pathological severity, gephyrin levels decreased with increasing severity until a moderate index was reached, and then increased, suggesting that higher gephyrin levels might compensate for excitotoxic damage in late stages of the disease. AD males showed a more pronounced reduction in gephyrin levels than AD females cf same-sex controls. A major splice variant of gephyrin was detected in all cases and in all three brain areas. This is the first study of gephyrin expression in AD.

BackgroundThe majority of established telestroke services are based on “hub‐and‐spoke” models for providing acute clinical assessment and thrombolysis. We report results from the first year of the successful implementation of a locally based telemedicine network, without the need of 1 or more hub hospitals, across a largely rural landscape.Methods and ResultsFollowing a successful pilot phase that demonstrated safety and feasibility, the East of England telestroke project was rolled out across 7 regional hospitals, covering an area of 7500 square miles and a population of 5.6 million to enable out‐of‐hours access to thrombolysis. Between November 2010 and November 2011, 142 telemedicine consultations were recorded out‐of‐hours. Seventy‐four (52.11%) cases received thrombolysis. Median (IQR) onset‐to‐needle and door‐to‐needle times were 169 (141.5 to 201.5) minutes and 94 (72 to 113.5) minutes, respectively. Symptomatic hemorrhage rate was 7.3% and stroke mimic rate was 10.6%.ConclusionsWe demonstrate the safety and effectiveness of a horizontal networking approach for stroke telemedicine, which may be applicable to areas where traditional “hub‐and‐spoke” models may not be geographically feasible.

Ann RC oll Surg Engl 2008; 90:6 01-605 601The explosion of internet usage by patients and the amount of healthcare information publicly available has led to new challenges for practising physicians. 1,2 The information available from at hird party has important implications for the doctor-patient relationship and can be used to enhance the healthcare experience. 2,3 Freedom of information on the internet dictates that anyone can publish information. Therefore, there is ar isk that such information, through ignorance or bias, may be incorrect or misleading. [4][5][6] Information of dubious quality or that is commercially motivated can be misleading, or even potentially lethal. 7,8 Many tools are available to assess healthcare information on the internet and, although there is consensus on key criteria, they are still being developed. 9-11 The LIDA Instrument is avalidated method of evaluating healthcare websites based on three important areas -a ccessibility,u sability and reliability. 12 Search engines are the most commonly used method to find information on the world wide web. Information exists about the usage characteristics of search engines in the UK. Ratings such as the Neilson'sN et rating 13 provide data for the most widely used search engines, and patterns therein. The five most visited search engines (Google, Yahoo, MSN, AOL and AskJeeves) field >9 0% of all search questions according to these surveys. Although searches often reveal thousands of links, at ypical user is likely to visit the most The aim of this studyw as to assess the quality of information available on the world wide web to parents of children undergoing tonsillectomy. HEAD &N ECK

Patients with malignant serotonin-producing carcinoid tumours in the jejunum, ileum and caecum generally have long survival expectancy. In some patients, however, tumour progression is more rapid and there is a need to identify them at an early stage. The purpose of this study was to determine if histopathological characteristics and/or Ki67 and apoptotic indices are of prognostic value in cases of metastatic disease. Eighty-one patients with this tumour were included in the study; all had metastases and their survival range was 1-223 months. Five growth patterns were identified and described. For 57 patients whose tumour material was available, the Ki67 and apoptotic indices were calculated for ten randomly selected tumour areas and 'hot spots'. A Cox regression analysis was used to test if histopathology and/or Ki67 index >/=1% could identify patients whose survival might be shorter than anticipated. One of the histopathological growth patterns-the solid (non-organoid) cell pattern-was correlated to shorter survival in both primary tumours and metastases, when compared with the organoid growth patterns (hazard ratio 2.9 and 2.3, p/=1%, in both primary tumour and metastases, identified patients at increased risk of shorter survival (hazard ratio 5.4 and 2.5, p/=1%, can be used to identify patients with a poorer prognosis. This study also showed that Ki67 index <2% cannot, as previously suggested, be used to indicate a benign progression for this tumour category.

Current treatments for osteoarthritis (OA) offer symptomatic relief but do not prevent or halt the disease progression. Chronic low‐grade inflammation is considered a significant driver of OA. Specialized proresolution mediators are powerful agents of resolution but have a short in vivo half‐life. In this study, we have engineered a Resolvin D1 (RvD1)‐loaded nanoliposomal formulation (Lipo‐RvD1) that targets and resolves the OA‐associated inflammation. This formulation creates a depot of the RvD1 molecules that allows the controlled release of the molecule for up to 11 days in vitro. In surgically induced mice model of OA, only controlled‐release formulation of Lipo‐RvD1 was able to treat the progressing cartilage damage when administered a month after the surgery, while the free drug was unable to prevent cartilage damage. We found that Lipo‐RvD1 functions by damping the proinflammatory activity of synovial macrophages and recruiting a higher number of M2 macrophages at the site of inflammation. Our Lipo‐RvD1 formulation was able to target and suppress the formation of the osteophytes and showed analgesic effect, thus emphasizing its ability to treat clinical symptoms of OA. Such controlled‐release formulation of RvD1 could represent a patient‐compliant treatment for OA.